1. Field
Embodiments disclosed herein relate generally to systems, devices, and methods for dissecting and analyzing tissues. More particularly, embodiments relate to high throughput imaging and laser dissection of frozen tissue samples.
2. Description of the Related Art
Diseases, such as cancer, are often identified by examining or analyzing tissue biopsies. Such tissue biopsies can contain multiple cell types that need to be identified in order to determine the proper treatment for the patient. Tissue dissection is a method to assist in isolating and removing specific cell populations from tissue samples. Normally, a tissue biopsy is removed from a patient and thin tissue slices are removed and analyzed under a microscope. In some cases, a tissue slice is stained, or treated with specific binding agents such as antibodies, to help a technician identify regions of the biopsy that are cancerous or atypical. In some cases, the tissue is digested in order to analyze expression of cellular components, such as nucleic acids or proteins.
Unfortunately, many of the experiments or stains used to identify the proper portion of a biopsy for further analysis may also materially change the biopsy tissue. For example, a technician may need to stain a sample in order to identify a cancerous region. However, the stain itself may degrade the proteins and nucleic acids in that region. Thus, the technician cannot easily identify or enrich for a cancerous population in a tissue biopsy prior to carrying out analysis of DNA, RNA, or other molecules.
The Cancer Genome Atlas (“TCGA”) is a project to catalogue cancer genomes. The TCGA requires tissue samples with a high percentage of tumor nuclei and low levels of cellular necrosis to be used for genetic analysis. Accordingly, it is desirable to isolate tumor-containing regions of tissue from undesirable regions prior to molecular extraction. It is possible to physically separate desirable regions of tissue. Tissue areas may be manually removed by a technician. However, this process may be inaccurate and high resolution removal may not be possible.
Another technique to physically separate desirable regions of tissue is laser capture microdissection (“LCM”). Using this technique, a technician may look through a microscope at a stained tissue sample mounted on a slide. A transfer film may be placed over the sample. Upon identifying a cellular region of interest the technician may active a laser. The laser may cause localized heating of the transfer film, thereby activating the film. The active film can have adhesive properties causing targeted cells or cellular regions to stick to the film above. These cells can then be removed and further analyzed. However, this process often requires the tissue to be at room temperature and for the tissue sample to be fixed, stained, and/or dehydrated. Accordingly, DNA, RNA, and other molecules may be degraded using LCM.